AB1416 INTERFERON SIGNALIZATION IN CHILDREN WITH JUVENILE SCLERODERMA
Authors: S. S. Kilic, H. Kose, A. Simsek, M. A. Kizmaz, T. Bozkurt, F. Ozturk, H. Saricaoglu, F. Budak
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background:</h3> <h3>Interferon Signalization in children with Juvenile Scleroderma</h3> Hulya Kose<sup>1</sup>, Abdurrahman Simsek<sup>2</sup>, Muhammed Ali Kizmaz<sup>2</sup>, Tugce Bozkurt, <sup>2</sup> Ferdi Ozturk<sup>3</sup>, Ferah Budak <sup>2</sup>, Hayriye Saricaoglu<sup>3</sup> Sara Sebnem Kilic <sup>1</sup> 1.Uludag University Faculty of Medicine, Department of Pediatric Immunology and Rheumatology 2.Uludag University Faculty of Medicine, Department of Immunology 3.Uludag University Faculty of Medicine, Department of Dermatology Juvenile dermatomyositis (JDM) is an inflammatory disease of the muscle, which is characterized by skin involvement, vasculitis, and progressive muscle weakness. Increased interferon signaling is thought to play a role in the pathogenesis of JDM and is associated with disease severity and activation, as well as the development of calcinosis. Juvenile scleroderma (JSc) is a heterogeneous group of diseases associated with sclerotic skin lesions, grouped together as systemic sclerosis and localized scleroderma (morphea). Although JSc has a different types of skin involvement than JDM, some similarities in their pathogenesis can be identified. <h3>Objectives</h3> The aim of this study is to measure the levels of cytokines and chemokines involved in interferon signaling in patients with JDM and JSc and to determine their correlation with disease severity. <h3>Methods</h3> Thirty-one JSc, 5 JDM, and 13 healthy controls were included in the study. Patients with morphea were scored according to the LoSCAT (activity index) and LoSDI (damage index) indices. Cytokines and chemokines involved in interferon gene signaling (IL -8, IL -1, IP-10, MCP1, TNF-α, CXCL-10, IFN-α, IFN-β, IFN-γ) and interferon signalizing genes including IFI27, IFI44, ISIG15, IFIT1, OAS1, RSAD2 were measured by ELISA and RT_PCR method respectively. <h3>Results</h3> The ratio of female to male patients was 24/12, the median age was 14 years (min 4, max 18), and the median follow-up time was 36 months (min 12, max 108). According to LoSCAT assessment of patients with JSc, the scores were mild 36% (n=13), moderate 25% (n=9), and severe 11% (n=4). Similarly, LoSDI assessment revealed mild 38% (n=14), moderate 22% (n=8), and severe 11% (n=4). It was found that IL-8, IFN-β, IP-10, and MCP-1 were significantly decreased in patients with JSc compared with the healthy control group. TNF-α and IFN-γ were found to tend to decrease in patients with JSc, whereas IFN-α tended to increase in patients with JDM. The correlation of LoSCAT and LoSDI indices with cytokine and chemokine levels in patients with JSc is summarized in Figure 1. In RT_PCR analysis of the interferon signaling genes, including IFI27, IFI44, ISIG15, IFIT1, OAS1, RSAD2, we found no statistically meaningful expressions of the genes compared with the healthy group. However, we identified the fold changes in RSAD2, IFI27, and IFIT1 in JDM and JSc patients compared with the healthy controls in the related genes. The fold changes of the interferon signaling genes are depicted in Figure 2. <h3>Conclusion</h3> The results suggest that interferon signaling may be impaired in patients with JDM and JSc, and that cytokines and genes whose significant changes were observed in this study may play a key role in monitoring disease activity. Repeating these studies with larger numbers of patients may shed light on the clinical pathogenesis. <h3>Reference</h3> [1] Kathryn S. Torok, Suzanne C. Li, Heidi M. Jacobe.Immunopathogenesis of Pediatric Localized Scleroderma.Front Immunol. 2019; 10: 908. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.